Chances and challenges of a long term data repository in multiple sclerosis: 20th birthday of the German MS registry - Nature
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OPEN Chances and challenges
of a long‑term data repository
in multiple sclerosis: 20th birthday
of the German MS registry
Lisa‑Marie Ohle1, David Ellenberger 1, Peter Flachenecker2, Tim Friede3, Judith Haas4,
Kerstin Hellwig5, Tina Parciak6, Clemens Warnke 7, Friedemann Paul8, Uwe K. Zettl9 &
Alexander Stahmann 1*
In 2001, the German Multiple Sclerosis Society, facing lack of data, founded the German MS Registry
(GMSR) as a long-term data repository for MS healthcare research. By the establishment of a network
of participating neurological centres of different healthcare sectors across Germany, GMSR provides
observational real-world data on long-term disease progression, sociodemographic factors, treatment
and the healthcare status of people with MS. This paper aims to illustrate the framework of the GMSR.
Structure, design and data quality processes as well as collaborations of the GMSR are presented. The
registry’s dataset, status and results are discussed. As of 08 January 2021, 187 centres from different
healthcare sectors participate in the GMSR. Following its infrastructure and dataset specification
upgrades in 2014, more than 196,000 visits have been recorded relating to more than 33,000 persons
with MS (PwMS). The GMSR enables monitoring of PwMS in Germany, supports scientific research
projects, and collaborates with national and international MS data repositories and initiatives. With its
recent pharmacovigilance extension, it aligns with EMA recommendations and helps to ensure early
detection of therapy-related safety signals.
Multiple sclerosis (MS) is the most frequent immune mediated disease of the central nervous system and the
most common cause of non-traumatic disability among young adults1,2. In 2015, the cumulative incidence of
MS in Germany was estimated at 18 new cases per 100,000 persons per year using public healthcare insurance
data2. The yearly prevalence of MS diagnoses has steadily increased but there are still uncertainties concern-
ing its aetiology3. The lack of legal reporting requirements for diagnosed MS cases and difficulties involved in
accessing routine medical data impede access to reliable information on MS prevalence and incidence, as well
as healthcare standards for persons with MS (PwMS) in Germany. Insufficient interoperability of different elec-
tronic healthcare record systems is another reason for the lack of a population-based database. A nationwide
MS registry with representative coverage of PwMS would offer the opportunity to monitor long-term disease
epidemiology and the health of PwMS. Furthermore, a national MS registry can contribute to data on disease
costs, cost–benefit-ratios, quality of healthcare, and patient-reported outcomes (PRO), which is important to
the evaluation of PwMS’s quality of life and to regulatory decisions4.
Treatment guidelines for chronic diseases like MS are often established based upon limited evidence regarding
the real-world efficacy and safety of disease modifying treatments (DMT)5,6. Additionally, long-term therapeutic
navailable7.
effects beyond the duration of phase III clinical trials, and treatment strategy studies are frequently u
1
MS Forschungs- und Projektentwicklungs-gGmbH (MS Research and Projectdevelopment gGmbH
[MSFP]), Krausenstr 50, 30171 Hannover, Germany. 2Neurological Rehabilitation Center Quellenhof, Bad
Wildbad, Germany. 3Department of Medical Statistics, University Medical Center Göttingen, Göttingen,
Germany. 4Deutsche Multiple Sklerose Gesellschaft, Bundesverband e.V. (German Multiple Sclerosis Society,
Federal Association), Hannover, Germany. 5Department of Neurology, Katholisches Klinikum, St. Joseph Hospital,
Ruhr University Bochum, Bochum, Germany. 6Department of Medical Informatics, University Medical Center
Göttingen, Göttingen, Germany. 7Department of Neurology, Medical Faculty, University Hospital of Cologne,
Cologne, Germany. 8Experimental and Clinical Research Center and NeuroCure Clinical Research Center, Max
Delbrueck Center for Molecular Medicine and Charité – Universitätsmedizin Berlin, Berlin, Germany. 9Department
of Neurology, Neuroimmunological Section, University Medical Center Rostock, Rostock, Germany. *email:
stahmann@msregister.de
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Considering the rapid development of DMT and the significant role of the diverse disease characteristics and
patient responses to and preferences in treatment, the documentation of complex individual treatment profiles is
becoming increasingly important for personalised treatment decisions that take into account individual disease
courses and patient preferences7–9.
Considering several observational studies indicating that early initiation and continuous use of highly effec-
tive DMT may reduce risks of long-term disability progression, there is a need for predictive tools to identify the
most beneficial treatment strategies9,10. Regarding these needs, registries can provide real-world data to support
physicians and PwMS in treatment decisions. Recent incidents of serious adverse events, like endocarditis11, or
multifocal leukoencephalopathy12 in PwMS on DMT highlighted the importance of standardised safety data
collection under real-world c onditions13. In 2017, the European Medicines Agency initiated a workshop bring-
ing together regulatory bodies, market authorisation holders, academics, and registry custodians to discuss the
extended use of MS registries for post-authorisation safety m onitoring14.
This article aims to show the framework and current setup of the German MS registry (GMSR), including
its methodology, technological infrastructure, and network as a reliable nationwide long-term data repository
and resource for registry-based trials.
Materials and methods
This article describes the governance, funding, and design of the GMSR. Its history, data collection processes,
description of datasets and data quality control mechanisms are outlined, and its research projects presented.
Descriptive analysis outlining the status of the GMSR was carried out using R Stat 4.0 (R Foundation, Vienna,
Austria). Data for descriptive analyses was extracted 8 January 2021. Data records that were locked due to e.g.
documentation errors and records with pending queries were excluded from analysis. Graphical representations
include histograms for expanded disability status scale (EDSS) distributions, scatterplots of patient demograph-
ics, and clinical characteristics at entry of the GMSR, including two-dimensional density estimates, shown as
contour plots (heat maps), and line charts of patients and visit frequency.
Results
The GMSR’s objectives. The GMSR aims to provide a reliable long-term data repository for transpar-
ency in epidemiology, demographics, disease characteristics, healthcare access and quality of care of PwMS in
Germany, and may be used to monitor improvements of healthcare15. It also implements and supports scientific
research projects such as registry-based (randomised) controlled trials and collaborations with other (inter-)
national repositories in a modular fashion16. One of its emerging objectives is the collection and reporting of
real-world safety data on disease modifying drugs.
The GMSR’s design. The GMSR established a network of participating centres across different healthcare
sectors in Germany (see Fig. 1). Centres that were accredited ‘MS Centre’, ‘Specialised MS Centre’, or ‘MS Reha-
bilitation Centre’ by the German MS Society participate in the GMSR documentation. Certificates are awarded
to university clinics, acute care clinics, rehabilitation clinics, MS outpatient clinics and resident neurologists
complying with specific criteria. Compliance is re-evaluated every 2 years17. With this certificate, each centre
commits itself to recruiting PwMS and collecting data for the GMSR. Physicians and other medical staff carry
out patient enrolment and data collection for the registry during routine examinations. After the provision of
written informed consent by adult PwMS (see Table 1), previous medical data can be collected, and prospective
data collection starts and is carried out until the patient’s death or withdrawal of informed consent.
Members of the medical staff enter data into a web-based electronic data capture (EDC) system. This system
allows a single patient’s data to be reported by multiple centres. To avoid duplicate patient entries, patient-
identifying data (first name, last name, sex, date of birth) is entered into the registry at enrolment and used to
generate a unique pseudonym. A trusted third party stores these pseudonyms and the corresponding identifying
data separated from the registry data. To guarantee patient privacy, only de-identified medical data is stored in
the registry’s database and used for analysis.
Data collection. In 2005, the registry started regular operations and has been continuously improved since
then. At first, data was collected through the ‘MSDS Klinik/Praxis’ software, which had been locally installed
in centres. Encoded datasets stored digitally were transmitted quarterly to the MSFP-gGmbH (MSFP) for qual-
ity checks and analysis. Since 2016, it is mandatory to document via the standardised web-based platform and
device-independent EDC-system ‘secuTrial’ and documentation through MSDS has been discontinued. The
web-based EDC-system is compliant with established tools and concepts of the Technology and Methods Plat-
form for Networked Medical Research e.V. (TMF) and is certified for conducting clinical trials (GCP, GAMP5,
FDA 21 CFR Part 11). PRO can be integrated to the system through patients uploading information themselves
through an app or web browser. Data entry happens directly through interfaces of the EDC system.
Governance of the GMSR. The GMSR is operated by the MSFP, a non-profit organisation founded in 2001
as a subsidiary of the German Multiple Sclerosis Foundation to develop and manage the registry on behalf of the
German Multiple Sclerosis Society. The governance of the GMSR includes a scientific advisory group of clini-
cians and representatives of MS centres as well as methodology experts (of medical statistics, epidemiology and
medical informatics), that approves and oversees scientific projects and research a ctivities18.
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Figure 1. Distribution of 187 MS centres participating in the GMSR across Germany. These include 70
specialised MS centres (red circle), 95 MS centres (orange triangle), and 22 MS rehabilitation centres (purple
cross). GMSR German Multiple Sclerosis registry. The map was created with R 4.0 based on data from gadm.org.
Inclusion criteria Exclusion criteria
Indefinable MS disease type (according to McDonald or Poser crite-
Age ≥ 18 years
ria) at date of inclusion
Written informed consent provided
Diagnosed MS (according to the applicable McDonald or Poser crite-
Inability to give informed consent
ria) with definable disease type or clinically isolated syndrome (CIS)
Primary residence in Germany
Table 1. Inclusion and exclusion criteria of the GMSR. CIS clinically isolated syndrome, MS multiple sclerosis.
Ethical considerations/registration. The GMSR was first approved by the ethics committee of the Julius-
Maximilians-University of Würzburg (number of vote 142/12). After switching to a web-based documentation
system, it received further ratification from ethical committees such as the Thuringia state chamber of physicians
and other universities.
Before inclusion to the MS registry, patients are informed about its conduct by medical staff and must provide
written informed consent before data collection can commence. Within this consent, patients can allow their
data to be used for further research activities. Data collection, storage and analysis are conducted according to
current European and national legislations for data protection.
The GMSR is registered at the German registry of clinical trials with registration number DRKS00011257,
and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance with reference
number ENCEPP/DSPP/21378.
History of GMSR. The history of the GMSR is described in Supplementary Document 1.
Dataset. In 2014, the GMSR’s dataset was revised to fulfil the increased requirement for harmonization and
comparability of data of different data sources. As a result, the dataset is a combination of datasets of the Ger-
man Multiple Sclerosis Society and the German Competence Network Multiple Sclerosis. The current minimal
dataset (see Supplementary Table 1) contains information on disease onsets, diagnoses, MS disease c ourses19,20,
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Dataset description
Inclusion and exclusion criteria
Informed consent
Scope of consent
Sex
Date of birth
Diagnostic criteria (McDonald, Poser)
Patient profile Disease onset
Date of diagnosis
Initial symptoms
Retrospective medical history data
Education
Occupation
Sociodemographic data
Family status
Residence
Disease course (lublin categories)
Expanded disability status scale
Disease status
MRI reports
Multiple sclerosis functional composite-index (Nine-hole peg test, PASAT3, 25-foot walk test)
Symptoms
Symptomatic therapy
Therapy
Prior and current disease-modifying treatment
Medicationa Treatment duration
Reasons for treatment discontinuations/switches
Type of care
(In)dependence
Medical aides
Relapse date
Relapses
Therapy
Comorbidities
Pharmacovigilance-Module* Adverse events
Pregnanciesa
Table 2. GMSR dataset. GMSR German multiple sclerosis registry, PASAT3 paced auditory serial addition
test (3 s-interstimulus interval). *Voluntary extended documentation, not collected by default. a The GMSR
cooperates with the German MS and child wish registry to allow follow up in more detail.
disabilities (as measured in EDSS and MS Functional Composite as well by MS Symptoms), disease activity,
MS therapy and socio-economic s tatuses21. In 2019, the GMSR dataset was extended by a pharmacovigilance
module to include documentation on medical history, body mass index, adverse events and pregnancies (see
Table 2). This documentation has been rolled out to eligible centres. The GMSR dataset is expandable regarding
new research questions and adapts to the specific requests of documenting parties using its dynamic web-based
EDC system and modular structure. Physicians schedule frequency of visits according to patients’ needs for
medical care and routine follow-ups, which the registry recommends to be carried out at least on an annual
basis. Relapses, adverse events, and pregnancies are documented as separate events.
Data quality. To constantly ensure high data quality, the GMSR established a wide range of quality control
measures. The web-based data entry system ensures that centres have the latest versions of questionnaires. Each
questionnaire is checked for consistency of dates, of value ranges and for plausibility. Branching logic (ask-
ing only relevant questions based on previous answers) ensures that data is only entered for applicable fields.
Furthermore, cross-reference-checks compare data between different questions and forms. Longitudinal checks
aim at preventing implausible data changes over time. Additionally, the registry uses R-Syntax for automated
quality control to find discrepancies and implausibilities. Participating centres receive findings through query
management system within the EDC-System. All data changes are recorded in audit trails. The database only
accepts records with the completed minimal dataset. Participating centres are provided with training materials
and tutorials. Yearly benchmarking reports include visualised comparative data, based on the centre’s population
versus other centres’ populations of the same type and individual feedback on data quality. Centres and MSFP
can execute ad-hoc statistics and reports as well as customised database searches at any time.
Data analysis. The GMSR conducts retrospective analysis for a variety of MS-related research questions.
These include demographic studies, measurements of care availability, causal inferences but also pharmacovigi-
lance studies and epidemiological assessments6,22–25. Most analyses are performed using R26. Before data is ana-
lysed, it is checked for duplicates, completeness, plausibility and consistency. The GMSR’s data is accessible at
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Figure 2. Number of recorded visits per years (by January 2021). Total (cumulative) number of patients
included in the GMSR by the end of each year is shown by the black solid line, while the number of patients
with actual baseline or follow-up visits during the resp. year is shown by the dashed line. The number of visits
per year is show as bars, distinguishing baseline and follow-up visits. GMSR German Multiple Sclerosis registry.
Number of visits Number of patients
Total 196,632 33,174
History of onset and diagnosis (dates) – 29,019
Education 121,155 27,172
Employment 154,394 28,677
Family 178,794 31,096
Nine-hole peg test 30,019 8194
25-foot walk test 17,829 7808
EDSS 201,712 33,059
MRI 35,427 18,318
DMD (y/n) 164,660 31,734
Current MS-symptoms* 172,032 32,277
(In-)dependence** 165,204 31,597
Table 3. Number of patients and visits by scale/category of information. DMD disease modifying drugs,
EDSS expanded disability status scale, MRI magnetic resonance imaging. *Fatigue, paresis, bowel and bladder
disturbances etc. **Care settings and the prescription/use of aids.
reasonable request by any qualified investigator under terms and conditions of the registry’s use-of-access poli-
cies and subject to informed consent of patients. Requests for research projects can be proposed via an applica-
tion form on GMSR’s website18.
Status quo. As of January 2021, 187 centres of all healthcare sectors throughout Germany participate in
the GMSR, and the new registry database includes documentation of more than 196,000 consultations of more
than 33,000 PwMS. Figure 1 shows the geographic distribution of participating centres across Germany. 5% of
registered patients were reported by multiple centres. Recent estimations based on the claims data of participat-
ing centres put the number of PwMS treated annually by the participating centres at approximately 90,000. Thus,
covering about one-third of the German MS-population (estimated at 240,000–250,000).
At time of data extraction, the yearly documentation for 2020 included 26,491 visits of more than 13,000
patients, with an average of two consultations per patient per year (see Fig. 2). 3530 patients joined the registry
in 2020. Table 3 shows the number of visits in which specific (sets of) variables are present.
In total, more than 33,000 PwMS were included in the MS Registry since 2014. Baseline data separated by
disease course as well as the current distribution of EDSS scores of patients are presented in Supplementary
Table S2 and in Fig. 3. In 2020, 4% of visits were documented by rehabilitation centres, 43% by MS centres and
53% by specialised MS centres. By January 2021, 75% of queries on visits data of 2020 were answered and closed.
The average time for a final response to a query was 4 (± 7) months (median 1 month) and 81% of all queries
were answered.
The GMSR baseline demographic data is comparable to recent publications based on German statutory health
claims data regarding female to male ratios, most affected age groups and geographical distribution. The age
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Figure 3. Current EDSS distribution among patients (n = 33,059) in the GMSR. EDSS expanded disability
status scale, GMSR German Multiple Sclerosis registry.
German MS registry Italian MS r egistry22 Danish MS r egistry23,24 OFSEP25 Swedish MS registry26
Female 71% 67% 69% 71% 70.3%
Age at onset (years) 33.1 ± 10.7 30.5 ± 10.5 32.6 ± 10.8
CIS 1.8% 5.6% 2.4% 12.1%
RRMS 75.8% 75.3% 80% 55.2% 67.5%
SPMS 15.7% 12.9% 12.7% 21.4% 24.6%
PPMS 6.7% 6.1% 4.8% 11.2% 7.9%
Table 4. Comparison of patient characteristics. Patients with unknown disease course are excluded. CIS
clinically isolated syndrome, MS multiple sclerosis, OFSEP observatoire français de la sclérose en plaques,
PPMS primary progressive MS, RRMS relapsing–remitting MS, SPMS secondary progressive MS.
and disease duration of PwMS at registry entry are presented in Supplementary Figure 1. Compared to Euro-
pean MS registries, there are differences in reported percentages of secondary progressive MS (SPMS) within
the registry’s population, whereas the differences in EDSS are narrower. Wider DMT options for patients with
eurologist27. Table 4
relapsing–remitting MS (RRMS) may be the reason for a bias in classification by the treating n
compares baseline GMSR patient data with data from the registries of Italy, Denmark, France, and S weden28–32.
Funding. The establishment and maintenance of the GMSR is funded by the German Multiple Sclerosis
Foundation and the German Multiple Sclerosis Society. Additionally, the MSFP has received financial support
from Biogen, Bristol Myers Squibb, Merck Serono, Novartis, Roche and Sanofi for the specific purposes of oper-
ating the GMSR. Principles of the cooperation between MSFP and pharmaceutical companies are: (1) Transpar-
ency: each stakeholder gets the same information at the same time and the type and scope of sponsorship is
made public, (2) Financing: to avoid an increased influence of a single stakeholder or a financial dependence on
one funder, stakeholders contribute equal amounts, regardless of the company’s market share, (3) Information
exchange: stakeholders meet at least once a year to discuss results, ideas for scientific evaluations and further
joint activities, (4) Scientific independence: the MSFP has the right to publish registry results independently.
Registry‑based studies and sub‑cohorts. Besides the operation of the MS registry, the MSFP develops
and provides the EDC system for MS research projects that can (partly) be linked to registry data (see Supple-
mentary Table 2)33.
Discussion
The GMSR is a unique and reliable long-term data repository for real-world data on epidemiology and health
of PwMS in Germany. It allows long-term monitoring of the disease course, analysis of different treatments and
evaluation of the comparative efficacy, effectiveness and safety of an increasing number of DMT, which cannot
be addressed as much by randomised clinical trials (RCT)10,24,34. The GMSR holds data on all approved DMT
instead of focusing on specific drugs24. In RCT, inclusion criteria often do not fit the effect mechanism of the
active substance, for instance, patients with low disease activity or long disease duration are included in studies
on high anti-inflammatory effect substances7. Their high costs and intensity result in their rather short duration
and insufficiency concerning real-world effectiveness in the long-term1,7. Therefore, registry data is important for
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patients, physicians, industry, regulatory authorities and health insurance system to provide support to treatment
decisions and the development of health promotion m easures5,10.
The increasing number of DMTs leads to individual treatment decisions, which consider disease related
variables like symptoms or clinical findings, but also patient preferences. The evaluation of the severity and
significance of specific patient symptoms and their consequences for disease management are often different
from that of physicians35. Consequently, PRO will become more important3,7. The technical infrastructure of
the GMSR allows implementation of PRO measurement via eCRFs that can be completed directly by patients
and is directly linked to medical data36.
The creation of an added value within the GMSR for health professionals to document disease progression
and treatment history directly through the EDC system, like automatically generated discharge letters and medi-
cal reports, could encourage them to participate in the MS registry and is constantly pursued by the GMSR. A
technical interface to the centre’s primary information system could have a similar effect due to the reduced
documentation effort. It could furthermore establish a documentation system for several different prospective
studies and reduce time and costs expenditure in the future. Despite its positive effects, the reuse and integration
of electronic healthcare records for research purposes is still in its early s tages37.
To increase follow-up rates, it is necessary to provide an incentive for participating centres to document visits
regularly. Possible incentives which are offered by the GMSR to achieve this goal are financial compensation,
requirements analysis at annual user meetings and guidance documents for follow-up processes.
Over the years, the GMSR’s findings have benefited MS science. The monitoring of PwMS through the registry
allowed for the first-time estimates concerning its prevalence, disease types, symptoms and degree of sympto-
matic treatment. Furthermore, the registry enables register based RCTs and General Data Protection Regulation
compliant patient recruitment.
Recently, evaluations of registry data on symptom frequency and symptomatic treatment patterns showed
that fatigue is one of the most common symptoms. This has only been analysed in smaller c ohorts38 but is of
high importance as fatigue impacts patients well-being and employment30. Through GMSR’s participation in
international projects, insights and comparison of data of PwMS from other countries and healthcare systems,
such as employment statuses23, time until the initiation of a DMT22 and validation of secondary progressive MS
classification methods39 were gained.
However, the GMSR suffers from certain biases and limitations. The registry is not population-based. To date,
there is no legal obligation to report MS cases in Germany. The introduction of an obligation would contribute
to completeness of the registry’s data and nationwide coverage. PwMS are treated in all areas of care (e.g. general
practioners, urologist etc.) and are therefore not always seen regularly in a specialised neurologic unit, thus a legal
obligation like in cancer would ensure the completeness. As the registry focuses on neurological care providers
of special experience in the treatment of PwMS, the proportion of clinically diagnosed RRMS cases is higher
than presented in the German statutory claims data. Our estimations show that since its revision in 2014, the
registry has captured more than 33,000 PwMS resulting in about one-third of the PwMS seen in the participating
centres. If data from the prior registry data collection, commenced at the turn of the century, is included, the
coverage of the GMSR reaches more than 73,000 PwMS. On annual basis the participating specialised centres
treat roundabout one-third of the prevalent German MS-population. Especially PwMS suffering from progres-
sive disease courses tend to seek neurological expertise less often, possibly explaining their underrepresentation
in the GMSR. However, by including PwMS from specialised rehabilitation centres, the GMSR still captures a
higher percentage of the progressive patients than if it would just recruit from outpatient facilities40.
Recent research on the conversion of RRMS into SPMS within the GMSR and other registries showed that
significant amounts of patients might be clinically labelled as RRMS while still receiving DMTs although objec-
tive algorithms would judge the disease course differently27.
With legal barriers in place that make the inclusion of under-age PwMS quite challenging and specific pae-
diatric data collections already in place it was decided in the conception phase of the GMSR to allow registry
entry only to adult PwMS. Paediatric MS patients are often treated in different settings than adult MS-patients.
However, the informed consent allows the collection of retrospective data from patients and paediatric onset
MS patients are included after their 18th birthday in the G MSR41,42.
With no public funding for maintaining a long-term operation of a data source like the GMSR, funding
remains a challenge that cannot be solely covered by the patient society. The GMSR has therefore started to
involve the industry for funding. The extension of the dataset by the pharmacovigilance module was an important
step for the use of registry data in non-interventional PASS, which was promoted by the E MA43. This may reduce
costs, increase transparency, and create confidence in the value of pharmacotherapy of MS.
Received: 31 March 2021; Accepted: 15 June 2021
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Acknowledgements
We would like to thank all the patients who gave their informed consent. Furthermore, this study would not
have been possible without the efforts of the centres participating in the registries. The centres are listed in the
Supplement.
Author contributions
L.M.O. substantially contributed to the conception, to the study design and to the data interpretation. She
drafted the manuscript and critically revised the completed final draft for important intellectual content. D.E.
substantially contributed to the conception, to the study design and to the data interpretation. He conducted
the statistical analysis and critically revised the completed final draft for important intellectual content. P.F.,
Scientific Reports | (2021) 11:13340 | https://doi.org/10.1038/s41598-021-92722-x 8
Vol:.(1234567890)www.nature.com/scientificreports/
T.F., J.H., K.H., T.P., C.W., F.P. and U.K.Z. critically revised the completed final draft for important intellectual
content and contributed to the revision. A.S. substantially contributed to the conception, to the study design and
to the data interpretation. He supervised this study and critically revised the completed final draft for important
intellectual content.
Funding
The German MS Registry of the German MS Society was initiated and funded by the German MS Foundation and
the German MS Society in 2001. It is operated by a not-for-profit company, the MSFP. In 2021, Biogen, Celgene
(BMS), Merck, Novartis Roche and Sanofi are participating in the multi-stakeholder funding approach to support
the registry’s operation and to allow the collection and reporting of data required as part of the EMA-minimal
data set. Industry funding does not result in restrictions to publishing data, nor do the funders have access to
the raw data or have any influence over the scientific conduct of the registry.
Competing interests
Lisa-Marie Ohle reports no disclosure relevant to the content of the submitted manuscript, her work on the
project was funded by a grant from the innovation fund of the German Federal Joint Committee (01VSF18038).
David Ellenberger reports no disclosure relevant to the content of the submitted manuscript. Peter Flachenecker
has received speaker’s fees and honoraria for advisory boards from Almirall, Bayer, Biogen Idec, Celgene, Gen-
zyme, Novartis, Merck-Serono, Roche and Teva. He has participated in pharmaceutical company sponsored trials
by Roche. None resulted in a conflict of interest. Tim Friede has received personal fees for consultancies (includ-
ing data monitoring committees) in the past three years from Bayer, Biosense Webster, Boehringer Ingelheim,
Cardialysis, CSL Behring, Daiichi Sankyo, Enanta, Fresenius Kabi, Galapagos, Janssen, Liva Nova, Novartis,
Parexel, Penumbra, Roche, SGS, Vifor; all outside the submitted work. Judith Haas reports no disclosure relevant
to the content of the submitted manuscript. Kerstin Hellwig reports no disclosure relevant to the content of the
submitted manuscript. Tina Parciak reports no disclosure relevant to the content of the submitted manuscript.
Friedemann Paul has received speaking fees, travel support, honoraria from advisory boards, and/or financial
support for research activities from Bayer, Novartis, Biogen, Teva, Sanofi-Aventis/Genzyme, Merck Serono,
Alexion, Chugai, MedImmune, Shire, German Research Council, Werth Stiftung of the City of Cologne, German
Ministry of Education and Research, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy
Jackson Charitable Foundation, and National Multiple Sclerosis of the USA. He serves as academic editor for
PLoS ONE and associate editor for Neurology, Neuroimmunology and Neuroinflammation. None resulted in a
conflict of interest. Clemens Warnke has received institutional support from Novartis, Alexion, Sanofi-Genzyme,
Biogen, Janssen, and Roche. Uwe K. Zettl has received speaking fees, travel support and /or financial support for
research activities from Alexion, Almirall, Bayer, Biogen, Bristol-Myers-Squibb, Janssen, Merck Serono, Novartis,
Octapharm, Roche, Sanofi Genzyme, Teva as well as EU, BMBF, BMWi and DFG. None resulted in a conflict of
interest. Alexander Stahmann has no personal pecuniary interests to disclose, other than being the lead of the
German MS Registry, which receives funding from a range of public and corporate sponsors, recently including
The German Innovation Fund (G-BA), The German MS Trust, German MS Society, Biogen, Celgene (Bristol
Myers Squibb), Merck Serono, Novartis, Roche and Sanofi. None resulted in a conflict of interest.
Additional information
Supplementary Information The online version contains supplementary material available at https://doi.org/
10.1038/s41598-021-92722-x.
Correspondence and requests for materials should be addressed to A.S.
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